Project Summary/Abstract Preclinical Alzheimer's disease clinical trials enroll cognitively normal participants who are willing to undergo disease biomarker testing, learn the results, and take an investigational drug (or placebo) if those results indicate that they are at increased risk for disease. Like traditional trials in Alzheimer's disease dementia, these trials require participants to enroll with a study partner, a person who can attend visits with the participant and report about any changes in the participant's cognitive or functional ability. Like traditional trials in Alzheimer's disease dementia, these trials face logistical challenges related to difficult recruitment. We recently showed that the requirement for a participant to learn their Alzheimer's disease biomarker status was not a barrier to successful recruitment. In contrast, the requirement of enrolling with a study partner was a significant barrier to participation for many potential enrollees. We also observed results that suggested that the study partner barrier was related to the requirement of biomarker testing and disclosure. This project will further investigate the study partner role in preclinical Alzheimer's disease clinical trials. First, we will explore the ethical implications of the study partner requirement, specifically whether this requirement is a barrier to enrollment because participants are unwilling to share their biomarker results with others. Second, we examine the scientific need for study partners, by measuring informants' accuracy and precision in assessing cognitive performance, predicting cognitive decline, and recognizing subtle changes in cognition, and comparing to participants' abilities to perform these roles themselves. These studies will provide valuable data toward improving preclinical AD trial protocol designs, assisting investigators making decisions around 1) whether to require study partners, 2) who is qualified to fill this role, and 3) how participants should be protected against potential stigma related to their eligibility.